Monohydroxyphenyl carbinols

ABSTRACT

Monohydroxyphenyl carbinols with at least two halogen atoms in the molecule have been found as microbicides which are effective against various types of bacteria and fungi.

United States Patent [1 1 Schellenbaum et al.

[ Nov. 11, 1975 MONOHYDROXYPHENYL CARBINOLS [75] Inventors: MaxSchellenbaum, Muttenz; Max

Duennenberger, Frenkendorf; Fulvio Casagrande, Binningen, all ofSwitzerland [73] Assignee: Ciba-Geigy AG, Basel, Switzerland [22] Filed:Feb. 26, 1975 [21] Appl. No.: 553,333

Related US. Application Data [62] Division of Scr. No. 164.446 July 201971, Pat No.

[30] Foreign Application Priority Data July 23. 1970 Switzerland11172/70 [52] US. 260/623 R; 424/347; 260/621 R; 260/621 K; 260/619 R[51] Int. CL' C07C 39/26 [58] Field of Search 260/623 R, 621 R, 621 K[56] References Cited UNITED STATES PATENTS 2.895.871 7/1959 Entemann .1260/618 B X 3.011069 12/1961 Wilkinson et all 260/621 K 3.092.639 6/1963Kulka 260/621 K Primary Examiner-James 0. Thomas, Jr. AssistamExaminer-W. B. Lone Attorney, Agent, or FirmFrederick H. Rabin [57]ABSTRACT Monohydroxyphenyl carbinols with at least two halogen atoms inthe molecule have been found as microbicides which are effective againstvarious types of bacteria and fungi.

7 Claims, No Drawings MONOHYDROXYPHENYL CARBINOLS This is a division ofUS. application Ser. No. 164,446, filed on July 20, 1971, now US. Pat.No. 3,879,477.

This invention relates to monohydroxyphenyl carbinols, their manufactureand use.

According to the present invention there are provided monohydroxyphenylcarbinols of the general formula wherein X is halogen,

X,, X and X are each halogen or hydrogen, and

R is a straight or branched chain alkyl group of l8 carbon atoms, orcycloalkyl group of 3-8 carbon atoms or phenyl, unsubstituted orsubstituted by halogen and/or alkyl of 1-2 carbon atoms, there being atleast 2 halogen atoms in the molecule.

These compounds possess microbicidal activity.

The hydroxyl group in formula I is preferably in 2- or 4- position. Themost important cycloalkyl groups are cyclopentyl and, especially,cyclohexyl.

The alkyl groups can be, for example, methyl, ethyl and all isomers ofpropyl, butyl, amyl, hexyl, heptyl and octyl. Halogen includes bromineand chlorine.

Formula 1 includes hydroxyphenyl carbinols of the formula C-Lll: I

wherein X is halogen and Alk is straight or branched chain alkyl of l-8carbon atoms, and X, X, and K, have the meaning given above, wherein thehydroxy group is in 2- or 4- position to the carbinol bridge.

In the compounds of formula 2 there are generally never more than 6halogen atoms.

Among the compounds of formula 3, the 2-hydroxyphenyl derivatives areparticularly notable. Preferred alkyl groups have 3-7 carbon atoms,these groups being preferably unbranched.

Particularly interesting microbicidal are those 2- hydroxyphenyl alkylcarbinols of formula 3 wherein X and X are the same and are chlorine orbromine, while X, and X, are hydrogen and Alk is n-butyl or n-amyl.

Furthermore, of great particular interest are monohydroxybenzhydrols ofthe formula wherein X, X,, X,, X,,, Y, Y and Y have the meanings givenabove and wherein at least two of X,, X,, X,,, Y, Y and Y, are differentfrom hydrogen.

Within the scope of fonnula 4 are compounds of particular interest andof the formula oa (m g O (01 by the formula U G q wherein p and q areeach 1, 2 or 3 and p +q is 3 or 4.

In order to manufacture the monohydroxphenyl carbinols of the invention,a ketone of the formula O x on" wherein X, X,, X X and R have themeanings given above is reduced. The compounds of fonnulae 2 to 6 can bemade from ketones of the formula x OH c x I x x Y4 -Alk (9) x' and 'wherein the various symbols have the meanings given above, and thenumbers of substituents and position of the hydroxy group are as givenabove also.

As reducing agent, for example a hydride can be used, the reaction beingcarried out in a solvent medium inert to the hydride.

For this, sodium borohydride is used with advantage,

generally 0.25 1 mol per mol of the hydroxyphenyl c (c1) (c1) a Thereaction temperature may vary for example between 0C and the boilingtemperature of the solvent used. The reaction time is correspondinglygenerally 20 to l hours.

Further reduction methods which can be used are reduction with zinc dustin alcoholic alkali hydroxide solution, for example potassium hydroxideor sodium hydroxide, and reduction by means of sodium amalgam inalcoholic solution or by means of aluminium isopropylate inisopropanolic solution (the method of Meerwein-Ponndorf-Verley) Noteshould also be taken of the catalytic hydrogenation of hydroxyphenylketones to give the hydroxyphenyl carbinols of the present invention.

The hydroxy'phenyl ketones used as starting products are known (seeBelgian patent specification nos.

753,533 and 753,534) or are manufactured by methods known per se, forexample from the corresponding benzoic acid or alkane carboxylic acidphenyl esters by the Fries reaction (compare Baltzly et al. Journal ofthe American Chemical Society 77, 2522 (1955 L. F. and M. Fieser,Lehrbuch der organischen Chemie l954, page 728 or G. A. Olah,Friedel-Crafts and Related Reactions 1964, page 499). The reaction cantake place in the molten state or in the presence of an organic solventmedium, e.g. nitrobenzene. On heating the corresponding phenyl estertogether with aluminum chloride there results themonohydroxybenzophenone or monohydroxyphenylalkyl ketone.

Particularly surprising for the compounds according to the invention isthe broad spectrum of anti-bacterial activity, which for most of thecompounds extends both over the area of gram-positive and gram-negativebacteria. From an application point of view, the lack of smell and thecolourlessness of the compounds of the invention is of particular value.

The present invention includes quite generally the use of the compoundsaccording to the invention in pest combating. The use of theanti-microbial compounds is possible on a very wide basis, particularlyfor the protection of organic substrates against attack by destructiveand pathogenic micro organisms (including phytopathogenic ones). Theanti-microbial agents noted are also suitable both as a preserving agentand as a disinfectant for technical products of all types, for plantprotection, in farming, in veterinary medicines and in cosmetictechnology.

The monohydroxybenzhydrols according to the invention are thus used fortreating or protecting organic materials, particularly textiles, byimpregnating at least one of these compounds into the material to betreated or protected or by applying such to the surface of thematerials.

Among non-textile technical products which can be preserved with the aidof compounds according to the invention, the following examples shouldbe noted:

Glues, binding agents, coating agents, textile dressings and treatingagents, printing and colouring pastes and similar preparations on thebasis of organic and inorganic dyes or pigments, also those whichcontain in admixture casein or other organic compounds. Also wall andceiling coatings, e.g. such as have an albumen containing colour bindingagent, are protected by addition of a compound according to theinvention from attack by pests. Use for wood protection is likewisepossible.

In the cellulose and paper industry also, the compounds according to theinvention can be used as conservation agents, inter alia for preventingthe known slime formation generated by micro organism infestation in theapparatus and machinery used for papermaking.

Furthermore by combination of the monohydroxybenzhydrols of theinvention with surface active agents, particularly washing active agentsit is possible to produce washing and cleaning agents with exceptionalanti-bacterial or anti-mycotic action. The compounds according to theinvention can, for example, be blended into soaps or combined withsoap-free washing agents or other surface active materials, particularlynon-ionic and cationic washing agents, or they can be combined togetherwith mixtures of soaps and soapfree washing materials, wherein in thesecombinations their anti-microbial effectiveness is retained to thefullest degree. By the use of aqueous preparations of such washing andcleaning agents containing monohydroxybenzhydrols according to theinvention, textile materials, for example, can be treatedanti-microbially during washing, since the active agent is substantiveto the textile material.

Cleaning agents which contain the compounds of the above noted formulaecan be used both in industrial and domestic use, also in foodstuffindustries e.g. dairies, breweries and slaughter houses. The presentcompounds can also be used as a component of preparations which are usedfor cleaning or disinfection.

The action of the monohydroxybenzhydrols according to the invention canalso be used in conserving and disinfecting preparations for plasticsmaterials. In the use of plasticisers it is advantageous to add theantimicrobial addition to the plastics material dissolved or dispersedin the plasticiser. It is advisable to take pains to obtain as even aspossible a distribution in the plastics material. The plastics materialswith anti-microbial properties can be used for useful articles of alltypes in which an effectiveness against varied germs, e.g. bacteria andfungi, is desired, thus for example in foot mats, bath curtainings,seats, steps in swimming baths, wall coverings, etc. By incorporationinto suitable waxing and polishing compositions, suitable floor cleaningand furniture care materials with disinfectant action can be produced.

Furthermore the compounds according to the invention can be used for theconserving and disinfecting treatment of fibres and textiles, whereinthey can be applied to both natural and synthetic fibres and thereeffect a permanent action against harmful (and pathogenic) microorganisms, for example fungi and bacteria. The addition of thesecompounds can take place therein before simultaneously with or after thetreatment of these textiles with other materials e.g. printing or dyeingpastes, dressings, etc.

Textiles treated in this way also are protected against the generationof a sweaty smell as is generated by micro organisms.

Treatment can take place for example by impregnating or spraying withsolutions or suspensions containing the above noted compounds as activeagent. The active agent can vary according to the purpose of use between0.1 and 5.0 grams active substance per litre, preferably 1-30 grams.

Generally textile materials of both synthetic or natural origin can besatisfactorily protected against attack by mould fungi or bacteria by acontent of from 0.1 to 3% of active agent. The active agent noted can beadded together with other textile treatment agents as dressing agents,permanent creasing treatments etc.

The ways of using the active agents of the present invention cancorrespond to the usual formulations for pest control agents, forexample, agents which contain the said active agent can optionally alsocontain additives such as solvents, dispersing agents, wetting agents,adhesives, light protection agents, optical brighteners etc., togetherwith other pest control agents, such as fungicides and bactericides.Particularly, however, as well as the active agent according to theinvention, the agent can contain a further solid or liquid thinningagent or a solid or liquid carrier. The invention extends tomicrobicidal agents which contain compounds of the general formula I.

The following examples will serve to illustrate the invention.

EXAMPLE 1 A. To a solution of 1.2 grams sodiumhydroxide in ml water and50 ml methanol there was added 9.0 g 2- hydroxy-5,3',4'-trichlorobenzophenone and 0.6 g sodiumborohydride. The reactionsolution was kept for 5 hours at 25C with stirring. After addition of 50ml 2-nhydrochloric acid the product was extracted with ethyl acetate andthe extract washed first with saturated potassium bicarbonate solutionand then with water. The extract dried over sodium sulphate left behind8.6 g of the compound of formula which was an oil which crystallized onstanding; melting point 120-l28C.

The purified compound from recrystallisation from chloroform melted atl30-l3lC. The pure yield amounted to 7.3 g.

B. To 31 g aluminiumisopropylate in 150 ml isopropanol there was added asolution of 9.0 g 2-hydroxy- 5,3,4',trichlorobenzophenone in 25 mlisopropanol. The reaction mixture was then boiled under reflux forhours. After the addition of 150 ml 2-n-hydroch1oric acid at C, theproduct was extracted with ethyl acetate and the extract washed firstwith saturated potassium bicarbonate solution and then with water. Fromthe extract which was dried over sodium sulphate there remained afterthe removal of the solvent 8.5 g of the compound 100 as an oil whichcrystallised on standing.

After recrystallisation from chloroform the compound was present in pureform and melted at l-l3lC.

1n the same way as example 1 or according to one of the other methodsgiven above the following compounds can be prepared which are shown inthe following table A:

TABLE A Com- Melting pound point No. R, R, R, R; R, R R R, R in "C 100CH H H C1 H H C1 C1 H 131 132 101 CH H H C1 H H Cl H H 102-104 1112 OH HCl H H H C1 H Cl 30 103 OH Cl H Cl H H C1 C1 H 155 157 104 OH H H Cl H HCl H Cl 110- 112 105 OH Cl H Cl H H Cl H H 93 94 1116 OH Cl H C1 H H ClH C1 106 107 107 OH C1 H C1 C1 H Cl H Cl 133 134 1118 OH (1 H C1 C1 H ClH H 176 178 TABLE A-contmued Com- Melting poun point No R. R, R;, R. R11.. R-, R. R in c 109 OH H C1 H C1 H C1 C1 H 145 146 110 OH H C1 H H HC1 C1 H 106-107 111 OH C1 H C1 C1 H Cl C1 H 189 19(1 112 OH H H C1 C1 HC1 (1 H Oil 113 OH H H Br H H C1 C1 H 134-135 114 OH Br H Br H H C1 C1 H124 125 115 OH H Cl H C1 C1 C1 H H 135-136 116 OH H C1 C1 H C1 C1 H H119- 117 OH H H Br H C1 (1 H H 103-104 118 OH Br H Br H C1 C1 H H 278279 119 OH H C1 H C1 C1 H C1 H 146 147 120 OH H C1 H H Cl H C1 H 135 136121 OH C1 H C1 C1 C1 H Cl H 156 157 122 OH H C1 C1 H C1 H C1 H 182-183123 OH H C1 H C1 C1 H H C1 175 176 124 OH C1 H C1 C1 C1 H H C1 189 -190125 OH H C1 C1 H C1 H H C1 156 157 126 OH H C1 C1 H H Cl H H 911 99 127OH H Cl H C1 CH H H H 115-116 128 OH H C1 H H CH H H H 131-132 129 OH ClH C1 C1 CH H H H 153 154 130 OH H C1 H C1 C1 H H H 99 100 131 OH H C1 HH C1 H H H 114-115 132 OH H H C1 H C1 H H H 97 9B 133 OH Cl H Cl H C1 HH H 78 79 134 OH C1 H C1 C1 C1 H H H 123 124 135 OH H C1 C1 H C1 H H H109- 110 136 OH Cl H C1 H H H H H 94 95 137 OH C1 H C1 C1 H H H H 168169 138 OH Br H Br H H H H H 121-122 139 OH C1 H C1 C1 H CH H H 175 176140 01-1 C1 H C1 C1 H Br H H 178 179 141 01-1 Br H Br H H Br H H 135 136142 OH H H Br H H C1 H H 105 106 143 OH Br H Br H H C1 H H 116-117 144 HH OH C1 H C1 C1 H H 144 145 145 H C1 OH C1 H H C1 H H 165 167 146 H C1OH C1 H H C1 C1 H 175 176 147 H Cl OH C1 H H Bl H H 159 160 148 H C1 OHH C1 H C1 C1 H 147 148 149 C1 H OH H H C1 C1 H H 159 160 150 H C1 OH H HH C1 C1 H 121 122 151 H Cl OH Cl H H H H H 144-145 152 H C1 OH Cl H C1C1 H H 162 163 153 H C1 OH Cl H CH H H H 158 159 154 H Cl OH Cl H Cl H HH 139 140 H C1 OH H C1 C1 H H H 176 177 156 C1 H OH H C1 H C1 C1 H 197198 EXAMPLE 2 fully. This was filtered off, washed with water, dried andrecrystallised once from methylene chloride-hexane for purification;melting point 130-l31C. The Pure yield amounts to 5.2 g.

1n similar fashion the compounds given in the following table B can beprepared. The general formula for compounds of table B is:

2 E OH I (II) A- H l TABLE B CompoundA ZI Z, Z3 Z4 Melting point No. inC 200 cH,- c1 H c1 H 55.5-56.5 201 cH H c1 01 H 84-85 CH3 Br H Br H82-835 202 203 CH;, C1 H 01 Cl 100-101 204 CH3-CH2 Br H Br H 63-64 205CH- ,CH,-CH2- (:1 H c1 H 45-46 206 CH3-CH2 CH,- Br H Br H 60-6] 207 CHCH -CH, H c1 Cl H 64.5-65.5 208 CH;,CH,-CH,- H C] H c1 94 9s 209cH,-cH,-cH, c1 H c1 (:1 130-131 210 CHn(CH2)r--CH Cl H c1 H 4849 211 CH,H c1 H CI 77.5-78.5 212 CH3CH, (:1 H 01 H 4647' 213 CH5CH,- H c1 H Cl102-103 CH;,\ 214 /CH c1 H C! H 5445 4 215 cH icH,), cH, (:1 H c1 H49-50 216 CH .,(CH,),CH, Br H Br H 66.5-67.5 217 cH.-(cH,), cH.- H c1 c1H 69.5-70.5 218 cH.-(CHr),CH,- H G H 01 77 7a 219 CH=,(CH2),CH, 01 H Cl01 108-109 220 cH,-(cH, ,-cH, (:1 H 01 H 011 221 CH=,-(CH Br H Br H64-65 tit-C 1- 222 CH (CH,) CH H C: H c1 64-65 223 CH;(CH1)nCH,- Cl H c1c1 66.5-67.5 224 CH (CH,)rCH (:1 H c1 H 011 225 CH -(CH, .-CH,- H Cl HC1 75.5-70.5 226 CH;,(CH,),CH, H c1 H c1 73-74 EXAMPLE 3' TABLEC-continued Determination of the Minimum Inhibiting Minimum ggggg5353322 3 12 3" smvhvlomccus Concentration (MIC) Against Bacteria andMoulds by the Gradient Plates Test Nos. (1) (2)++ (impound MIC PP'" MICGradient test 1 is given by W. Szybalski et al., Scif ence 116, 26(1952). 104 20 119 0.4 Gradient plate test 2 is that given by Nuesch and:82 g 3 1 Knuesel, Sideromycins, in the book by Gottlieb and )7 05 22Shaw Antibiotics, Mechanism of Action, volume 1 :33 8.3 8.; (1967),Springer Verlag. H0 5 The compounds of formulae 1 and 2 were mixed as111 1 126 4 suitable fom-tulations (e.g. as solutions in dimethylsulf-63 i oxide) of given concentration with warm bram heart H4 129 3infusion-agar (bacteria) or mycophil-agar (moulds). 130 3 14s 50 Theliquid mixtures were poured onto a solid wedgeg8 :19, shaped base agarlayer and likewise allowed to solldify. r 33 w 148 The test organism wasthen applied In a line perpeng :28 dicular to the gradient with apasteur pipette. After m- I 36 30 I52 25 cubation for 24 hours at 37C(bacteria) or 72 hours at 137 3 154 30 30C (moulds) the length of thebacteria which had g 5 -2 grown on the inoculation line was measured andex- 140 2111 35 pressed in parts per million of active agent. Theresults :2: are given in the following table C to F. 5 3 3 3 144 20 2060.3 TABLE.C 30 Minimum inhibiting concentration against Staphylococcusaureus (Bacteriostusis). U 1 Compound MIC in ppm Compound MIC in ppm s 115 0.4 515 20 101 30 116 2 216 10 TABLE C-continued TABLE E-continuedMinimum inhibiting concentration against Staphylococcus aureus(Bactcriostasis )1 Minimum inhibiting concentration against Aspergiiiusniger (Fungistasis)v MIC in ppm Compound MIC in ppm Compound MIC in ppmCompound Compound MIC in ppm TABLE D Minimum inhibiting concentrationagainst Escherichia TABLE F coli (Bucteriostusis). v Minimum inhibitingconcentration against Trichocompound MIC m Pp Compound MC ppm phytonmentugrophytes (Fungistasis).

ml H7 Com 0 nd MICi m Com ound MIC in m 102 20 119 20 p u n pp P W 10310 120 40 100 3 H6 2 104 122 15 101 10 117 10 105 35 120 10 102 10 11110.1 40 127 40 103 0.2 119 0.1 1011 30 1211 50 5 104 4 120 4 109 15 13020 4 121 4 110 20 131 70 106 2 122 4 111 20 133 00 107 1 123 02 112 25135 30 108 0.3 124 0 113 30 I36 66 110 4 125 4 114 30 137 40 111 0.3 1203 10 I38 50 30 112 3 127 3 110 20 140 30 113 3 1211 20 14 20 I I4 I i293 42 40 H5 0,4 130 I 143 30 131 10 1411 4 149 50 132 10 149 10 150 45133 4 150 5 154 50 35 134 1 151 30 150 50 135 7 152 10 201 50 130 10 15330 203 40 137 3 154 2 205 40 I38 3 155 10 200 35 139 2 150 4 207 40 1401 201 20 2011 30 40 141 1 203 4 209 30 142 5 204 10 213 30 143 3 205 30215 40 144 10 200 10 210 20 145 10 207 5 217 20 20B 2 218 I0 '1 7 :22 1045 5?: 5,, 212 0.5 213 5 215 20 2": 4 TABLE E 0 Minimum inhibitingconcentration against Aspergillus 5Q niger (Fungistasisi- Compound MICin ppm Compound MIC in ppm 100 30 119 10 223 2 101 60 50 224 3 102 40122 25 25 1 103 20 I26 30 55 22b 10 104 50 127 30 105 30 129 40 106 2025 1011 20 133 0 110 30 45 EXAMPLE 4 111 20 130 60 i 112 40 1411 40 60 Aspecimen of g cotton-poplin was impregnated :3 at 20C for 7 minutes in abath of the foliowmg compo- 1 1o 1 5 144 711 smon: 117 55 20 1000 mlwater I48 15 2.7 mi cloth softening rinsing dye (containing 7% of 65 amixture of dl-octadecyl and di-hexadecyi-dime- 152 55 thylammoniumchloride) 15 mg of the compound of formula (109) (added as 5110 140 asolution in 0.5 mi dimethyisulfoxide) Two observations were made, thatof the zone of inhibition arising around the roundels (inhibition zonein mm) and the determinable growth above or below the cloth. Theinhibition zone was only a trace quantity while the determinable growthwas Similar effects were obtained with further compounds of formula l or2.

EXAMPLE For the manufacture of an anti-microbial tablet of soap, 2.4 gof one of the compounds of Formula 1 or 2 were added to the followingmixture:

120 g natural soap in flake form 0.12 g disodium salt ofethylenediaminetetraacetic acid (dihydrate) 0.24 g titanium dioxide.

The soap shavings obtained by rolling were powdered with a high speedmixture and then pressed to soap tablet form.

Concentrated aqueous solutions of the anti-microbial soaps were mixedinto warm brain heart infusion agar so that in-corporation dilution rosewith 2, 10, 20, 100 etc. parts per million active agent were produced.The warm mixtures were poured into petri dishes, allowed to solidify andthen infected with Staphylococcus aureus.

After 24 hour incubation at 37C the minimum inhibiting concentration wasdetermined. The results are shown in the following table. Similarresults were obtained by the use of other compounds of formulae l and 2.

Compound No, Minimum inhibiting concentration of the anti-microbial soupin p.p.m. active agent Specimens of 100 g cotton-cretonne wereimpregnated on the foulard with 1% solutions of compounds of formula 1in isopropanol at 20C and then squeezed out with 100% bath take-up.

In the same way, samples of 100 g wool cheviot were treated.

The textiles which were dried at 30 to 40C contained l% by weight ofactive agent taken on their own weight.

For testing the action against bacteria, roundels of mm diameter cutfrom the impregnated cloth, dewatered and watered, were laid for 24hours at 29C on brain heart infusion agar plates which had been previously infected with Staphylococcus aureus. The plates were thenincubated for 18 hours at 37C Two factors were observed: first, theinhibition zone (in mm) arising round the roundels and second, the mi-14 croscopically determinable growth (in under or on the cloth.

Results are expressed in the following table; similar results wereobtained also with further compounds of formulae 1 and 2 SubstrateCompound unwatered watered (with 1% active agent) lnhib- Growth lnhihGrowth ition (7c ition zone zone (mm) (mm) 103 8 0 9 0 I08 5 0 4 0Cotton 1 l5 9 0 5 0 I 16 8 t] 5 0 152 4 0 2 0 103 5 O 2 0 I08 3 O 4 0Wool I I5 6 0 5 0 l 16 5 0 5 0 [52 Trace 0 Z 0 EXAMPLE 7 SubstantivityTests with Calf-Hide Roundels determinable growth under or on theroundels was determined in Results are as follows:

Soap with Compound No. Inhibition zone in Growth in '71 Similar valueswere obtained using other compounds of formulae 1 and 2.

EXAMPLE, 8

The following mixture was milled on the twin-roll mill at C for 20minutes:

100.00 g polyvinylchloride 19.20 g di-(2-ethyl-hexyl-phthalate) 27.00 gdi-(2-ethyl-hexyl-sebacate) L50 g Ba/Cd-laurate 0.25 g Stearic acid 7.80g of a solution of 3.10 g of a compound of formula l in 4.70 gdi-(Z-ethyI-hexyI-phthalate) The roll separation was adjusted so that 1mm thick sheets were formed which were then pressed for 20 minutes atl65-l70C under a pressure of 1,400 kg/cm".

For testing the action against bacteria, discs of 10 mm diameter werestamped from the rolled soft polyvinylchloride sheet and laid onbrain-heart infusion agar plates which had previously been infected withStaphyloccocus aureus. The plates were then incubated for 24 hours at37C.

The zone of inhibition arising round the discs was measured in mm andthe microscopically determinable growth above and below the softpolyvinylchloride was 5. The compound measured in The results are givenin the following table: Similar action is observed with other compoundsof formulae 1 and 2. 0" Br EH Compound No. Zone of Inhibition Growth(/r) CH1l (CH2)Z! 'CH1 H 106 Truce l) I08 3 0 Br I l5 2 0 I56 2 O l 5 Weclaim: according to claim 3.

l. A compound of the formula X OH (Hi 6. The compound c Alk X I i"CH;,(CH- -l,-CH, H wherein each of X and X is halogen; each of X and Xis hydrogen or halogen; Alk is straight or branch chain alkyl havingfrom 1 to 8 carbon atoms; and the hydroxy group is in the 2 or4-position to the carbinol bridge.

2. A compound according to claim 1 wherein the hydroxyl group is in2-position to the carbinol bridge and Alk represents an unbranched alkylgroup with 3-7 Carbon atOmS- according to claim 3.

3. A compound according to claim 1 wherein X and X are the same and arechlorine or bromine, X and X are hydrogen and Alk is n-butyl or n-amyl.

4. The compound 7. The compound OH C l according to claim 3.

1. A COMPOUND OF THE FORMULA
 2. A compound according to claim 1 whereinthe hydroxyl group is in 2-position to the carbinol bridge and Alkrepresents an unbranched alkyl group with 3-7 carbon atoms.
 3. Acompound according to claim 1 wherein X and X'' are the same and arechlorine or bromine, X1 and X2 are hydrogen and Alk is n-butyl orn-amyl.
 4. The compound
 5. The compound
 6. The compound
 7. The compound